Robert Cade

Comparison of Azathioprine, Prednisone, and Heparin Alone or Combined in Treating Lupus nephritis

50 patients with proliferative glomerulonephritis due to lupus erythematosus were assigned in order of their chronologic appearance at the hospital alternately to treatment with either daily high dose

Autism and Schizophrenia: Intestinal Disorders

We examined Dohans hypothesis that schizophrenia is associated with the absorption of “exorphins” contained in gluten and casein. In addition, because of the work of Reichelt et al. (Reichelt, K.L., Saelid, G., Lindback, J. and Orbeck, H. (1986) Biological Psychiatry 21:1279–1290) and Rodriguez et al. (Rodriguez, Trav, A.L., Barreiro Marin, R, Galvez, Borrero, I.M., del Olmo Romero-Nieva, F. and Diaz Alvarez, A. (1994) Journal of Nervous and Mental Disease Aug; 182(8): 478–479), we carried out similar studies on a group of children with autism. In both syndromes we found similar patterns of peptide containing peaks (Ninhydrin positive) after molecular screening with Sephadex G-15. Immunoglobulin assay of IgA and IgG against gliadin and casein in serum was done. High titer IgG antibodies to gliadin were found in 87% of autistic and 86% of schizophrenic patients and high titer IgG antibodies to bovine casein were found in 90% of autistic and in 93% of schizophrenic patients. High titer IgA antibodies to gluten or casein were found in 30% of children with autism while in schizophrenic patients 86% had elevated IgA antibodies to gluten and 67% to casein; some normal children and adults have these antibodies but only in trace amounts. When schizophrenic patients were treated with dialysis or a gluten-casein free diet, or both (Cade, R., Wagemaker, H., Privette, R.M., Fregly, M., Rogers, J. and Orlando, J. (1990) Psychiatry: A World Prespective 1: 494–500) peptiduria and Brief Psychiatric Rating Scores fell while abnormal behavior diminished. A gluten-casein free diet was accompanied by improvement in 81% of autistic children within 3 months in most of the behavior categories. Our data provide support for the proposal that many patients with schizophrenia or autism suffer due to absorption of exorphins formed in the intestine from incomplete digestion of gluten and casein.

Effect of aerobic exercise training on patients with systemic arterial hypertension

One hundred five patients with established diastolic hypertension were enrolled in an exercise program to examine the effect of aerobic conditioning on blood pressure. In four patients, the decrease in mean blood pressure was less than 5 mm Hg; in all others, there was a significant decline in arterial blood pressure. In 58 patients who were not taking drug medication in the pre-exercise period, mean blood pressure decreased by 15 mm Hg. Of 47 patients receiving drug therapy during the pre-exercise period, 24 were able to discontinue all medication. Mean blood pressure in this group fell from 116.9 +/- 6.5 mm Hg to 97.2 +/- 9.2 mm Hg as a result of exercise. In patients still taking antihypertensive drugs, mean pressure decreased from 120.9 +/- 28.8 mm Hg to 104.4 +/- 17.9 mm Hg after three months of exercise. It is concluded that in patients physically and emotionally able to exercise, a significant decline in blood pressure can be achieved.

Angiotensinogen Gene Knockout Delays and Attenuates Cold-Induced Hypertension

Abstract—The aim of the present study was to assess our hypothesis that the renin-angiotensin system (RAS) is responsible for cold-induced hypertension and cardiac hypertrophy. Two groups of wild-type (WT) mice and 2 groups of angiotensinogen gene knockout (Agt-KO) mice (6 per group) were used. After blood pressures (BP) of the four groups were measured 3 times at room temperature (25°C), 1 WT and 1 Agt-KO group were exposed to cold (5°C). The remaining groups were kept at 25°C. BP of the cold-exposed WT group increased significantly in 1 week of cold exposure and rose gradually to 168±7 mm Hg by week 5, whereas the BP of the Agt-KO group did not increase until week 3. The cold-induced increase in BP (&Dgr;BP) was decreased significantly in the Agt-KO mice (19±3 mm Hg) compared with that of the WT mice (61±5 mm Hg) by 5 weeks of exposure to cold. Both WT and Agt-KO groups had cardiac hypertrophy in cold to the same extent. Agt-KO caused a significant increase in nitric oxide (NO) production. Thus, the RAS may inhibit NO formation. Chronic cold exposure decreased NO production, which may be mediated partially by activation of the RAS. These results strongly support that the RAS plays a critical role in the development of cold-induced hypertension but not cardiac hypertrophy. Moreover, the role of the RAS in cold-induced hypertension may be mediated in part by its inhibition on NO production. The findings also reveal the possible relation between the RAS and NO in cardiovascular regulation.

Prevention of Recurrent Urinary Tract Infections in Postmenopausal Women

Twelve postmenopausal women who experienced frequent urinary tract infections were found to have atrophic vaginitis. Four of them who were taking sulfonamide preparations chronically also had an interstitial nephritis manifest by decreasing glomerular filtration rate and eosinophiluria. Treatment consisted of a Betadine douche daily for 1 week, administration of an appropriate nonsulfonamide antibiotic, and institution of estrogen therapy to restore glycogen deposition in the vaginal epithelium and promote return of a normal vaginal pH and bacterial flora. Prior to estrogen therapy, the frequency of infection was four per patient per year. During a follow-up observation period ranging from 2 to 8 years, there have been only four infections in the entire group. When sulfonamides were discontinued in the 4 patients with manifestations of interstitial nephritis, the eosinophiluria cleared, and the glomerular filtration rate increased significantly.

Relation of β-casomorphin to apnea in sudden infant death syndrome

Sudden infant death syndrome (SIDS) is the most common cause of death in infants and its pathogenesis is complex and multifactorial. The aim of this review is to summarize recent novel findings regarding the possible association of beta-casomorphin (beta-CM) to apnea in SIDS, which has not been widely appreciated by pediatricians and scientists. beta-CM is an exogenous bioactive peptide derived from casein, a major protein in milk and milk products, which has opioid activity. Mechanistically, circulation of this peptide into the infants immature central nervous system might inhibit the respiratory center in the brainstem leading to apnea and death. This paper will review the possible relationship between beta-CM and SIDS in the context of passage of beta-CM through the gastrointestinal tract and the blood-brain barrier (BBB), permeability of the BBB to peptides in infants, and characterization of the casomorphin system in the brain.

Effects of phosphate loading on 2,3-diphosphoglycerate and maximal oxygen uptake.

Increased concentration of red blood cell 2,3-diphosphoglycerate (RBC 2,3-DPG) shifts the hemoglobin-oxygen dissociation curve to the right, thus theoretically allowing better oxygenation of tissues. To determine whether such a shift is physiologically significant, we investigated the effects of oral phosphate loading on several parameters including plasma phosphate concentration, RBC 2,3-DPG, hematocrit and hemoglobin concentration, maximal oxygen uptake (VO2max), and degree of lactic acidemia in 10 well-trained distance runners. After control determinations were made, either a phosphate load or a placebo was given for 3 d before the athlete was restudied. A placebo and two phosphate-loading studies were performed at weekly intervals, followed by 2 wk of rest and another post-intervention control study. Blood samples for control values were drawn before and after a standard warm-up period, after treadmill exercise at a 10% grade, and at the completion of the VO2 determination. After oral phosphate loading there was a significant increase in serum phosphate and RBC 2,3-DPG. Maximal oxygen uptake was significantly increased and correlated with the rise in RBC 2,3-DPG (r = 0.81). The increase in blood lactate after exercise on the 10% grade was attenuated during sessions which followed phosphate loading.

Role of central angiotensin II receptors in cold-induced hypertension.

BACKGROUND Earlier studies from this laboratory showed that central angiotensin II (AngII) receptors are upregulated by chronic cold exposure. The purpose of this study was to determine whether central AngII receptors may play a role in the development of cold-induced hypertension. METHODS Four groups of rats (six rats each) were used. Two groups were exposed to cold (5 degrees C) and the other two groups were kept at 25 degrees C. One cold-exposed and one warm-adapted group were treated chronically, via osmotic minipumps, with AngII type 1 (AT1) receptor blocker (losartan, 6.0 microg/2.5 microL/h, intracerebroventricularly) at the beginning of cold exposure. RESULTS Systolic blood pressure (BP) of the cold-exposed untreated group increased during week 1 of cold exposure and rose to 160+/-4 mm Hg by week 4, whereas BP of the losartan-treated group in cold did not increase and remained at 121+/-3 mm Hg. Cold-induced increases in drinking response to AngII, plasma renin activity, and urine norepinephrine output disappeared in the treated rats, indicating blockade of central AngII receptors. Withdrawal of losartan at 4 weeks resulted in an increase in BP of this group to the cold-exposed untreated level, which was accompanied by an increase in the above parameters. Significant increases in AngII-induced drinking response and hypothalamic AT1 receptor mRNA content of the cold-exposed rats indicate upregulation of AngII receptors during chronic cold exposure. Hypothalamic AngII level was not affected by cold exposure. CONCLUSION Upregulation of brain AT1 receptors plays a role in the development of cold-induced hypertension.

Hepatorenal syndrome. Studies of the effect of vascular volume and intraperitoneal pressure on renal and hepatic function

Eleven patients with well-documented hepatorenal syndrome were studied by measurement of blood volume, glomerular filtration rate, renal plasma flow, plasma aldosterone concentration, renin substrate concentration, and plasma renin activity. They were then given 750 ml of stored plasma, 750 ml of fresh frozen plasma, and then an infusion of angiotensin II, in random order on successive days. Infusion of fresh frozen plasma improved function more than did stored plasma and in addition returned a very low filtration fraction toward normal. Angiotensin II infusion increased filtration fraction, but decreased glomerular filtration rate, renal plasma flow, and urine flow sharply. Patients were then given a daily infusion of 1,000 ml of fresh frozen plasma for seven to 18 days to expand the blood volume to supranormal levels as assayed by serial measurement of blood volume. Plasma aldosterone levels decreased to a normal range, glomerular filtration rate and renal plasma flow both increased, and urinary excretion of sodium and potassium both returned toward normal. The effect of intraperitoneal pressure was then studied by measuring glomerular filtration rate, renal plasma flow, pressure in the vena cava, hepatic vein free flow, and hepatic vein wedged pressure before, during, and after paracentesis to reduce the intraperitoneal pressure from 30 to 40 cm H2O to 12 to 17 cm H2O. Venous pressures moved parallel to ascitic fluid pressures, and glomerular filtration rate, renal plasma flow, and urine flow all improved sharply; then, as ascitic fluid continued to form, reducing vascular volume, urine flow, glomerular filtration rate, and renal plasma flow all decreased slowly. Six patients then underwent placement of a LeVeen shunt. Improvement in glomerular filtration rate and renal plasma flow and clinical condition was dramatic. During postoperative observation of up to two years, progressive improvement in hepatic function has occurred.

Chronic renal vein thrombosis

Twenty-eight patients with demonstrated chronic renal vein thrombosis were studied. In seven, only small venous channels were involved; in 21, both small and large veins were thrombosed. A constellation of findings occurred with such frequency in these patients that we believe it virtually diagnostic of renal venous obstruction. These findings include the nephrotic syndrome, great variability in proteinuria and glomerular filtration rate, pulmonary embolization, sterile pyuria, hematuria, hyperchloremic acidosis, decreased renal tubular threshold for glucose and increased fibrin degradation products. These findings are an indication for definitive angiographic and biopsy procedures. Prolonged anticoagulant therapy was generally very effective.